Conjugation

First, let us learn what is metabolism of xenobiotics..

• Detoxification –

    The series of biochemical reactions occurring in the body to convert foreign compounds to non-toxic and more easily excretable form.

• Xenobiotic is any foreign or strange substance to the body.
• Detoxification of this is called metabolism of xenobiotics.
• The metabolism of xenobiotics is divided into 2 phases –

1. Reactions are – oxidation, reduction, hydrolysis.
2. Conjugation reactions.

Let us study conjugation in details.

Conjugation is a process in which a foreign substance combines with a substance produced in the  body.

The combined product is then easily detoxified & excreted from the body.

• Few examples of important conjugating agents –

1.Glucuronic acid :

• This is the most common.
• The active form of glucoronic acid is UDP-glucoronic acid in uronic acid pathway.
• UDP-glucuronyltransferasesare the enzymes which participate in glucuronide formation.
• It occurs with compounds containing hydroxyl , carbonyl, sulfhydryl or amino groups.
• Strongly acidic compounds which are more soluble in water are produced – hence more easily excreted.

2.Glycine

• Aromatic carboxylic acids are conjugated with glycine.
• When benzoyl CoA is conjugated with glycine, hippuric acid is formed.

3.Glutamine :

• Is relatively less important.
• Phenylacetic acid is conjugated with glutamine to form phenylacetyl glutamine.

4.Methylgroup :

• Methyl group of S-adenosylmethionine is used to methylate many compounds.

Enzyme methyl transferase is used.

5.Sulfate:

• The active form 3’-phosphoadenosine 5- phosphosulfate(PAPS)participates in conjugation.
• Enzyme sulfotransferase in involved.
• Aliphatic & aromatic compounds undergo sulfation.

6.Acetic acid :

-Acetyl CoA is the active form .

– Drugs like sulfanilamide are converted to acetyl derivatives.

7.Thiosulfate :

• Highly toxic cyanides are conjugated with thiosulfate to form less toxic thiocyanate.

8.Glutathione :

• Glutathione is a tripeptide.
• A wide range of organic compounds such as alkyl or aryl halides, alkenes and epoxides are conjugated with cysteine of glutathione.

• The conversion of bilirubin to conjugated bilirubin is an example of conjugation with glucuronide.
  • Bilirubin combines with UDP – glucuronic acid to form bilirubin-diglucuronide.

Contributed by

Soumya Khot- GMC, Kolhapur.